Electrochemical process and apparatus to control the chemical state of a material

ABSTRACT

Electrochemical process and apparatus to control the chemical state of a material, that is, to cause said material to retain desired characteristics in an environment that normally would cause a change in those characteristics or to cause a material that has deteriorated from a desired chemical state to revert to the desired state.

This is a division of application Ser. No. 636,290 now U.S. Pat. No.4,139,348, filed Nov. 28, 1975 and is being filed to comply with arequirement for restriction.

The present invention relates to electrochemical processes and apparatusfor controlling the chemical state of a material.

By way of background and to place reasonable limits on the size of thisdisclosure, the following publications are noted: Handbook ofBiochemistry, second edition, published by Plenum Press, 1973,containing papers delivered at an American Chemical Society Symposium,Chicago, 1973 and, in particular, the paper entitled "The Evolution ofMetals as Essential Elements [with special reference to iron and copper"by Frieden at pp. 1-30; Biochemistry, Lehninger, published by Worth,Inc., 1970, pp. 148-150; "Methemoglobin," Conant et al (1924), TheJournal of Biological Chemistry, Vol. LXII, No. 3, pp. 595-620;"Oxidation-Reduction Potentials of the Methemoglobin-Hemoglobin System,"Taylor et al (1939), published in The Journal of Biological Chemistry,pp. 649-622; The Pharmacological Basis of Therapeutics, of the editionpublished by MacMillan and Company (1970), pp. 1056-7 and 166a; The RedCell (Harris et al), p. 486, published by Harvard University Press(1970); "Emphores," Pardee, pp. 216 et seq. of Structure of Chemical andMolecular Biology, edited by Rich et al, published by Freeman, Inc.(1968); Advanced Inorganic Chemistry, Cotton et al, pp. 403-421 and801-1055, published by Wiley, Interscience (1972); Current DrugHandbook, pp. 74-76, published by Saunders Company (1974); andIntroduction to A Submolecular Biology, Szent-Gyorgi, Academic Press(1960).

The invention is multi-faceted. A common thread is that of renewing orrejuvenating materials that have for one reason or another changed (orwould change in the absence of countermeasures) to an undesired statefrom a desired state. Accordingly, the principal object of the inventionis to provide a system containing a material that is subject to achemical change, but in which the chemical state of the material iscontrolled.

One aspect of the invention is concerned with the detection of certainmolecular species wherein a material characteristic such as, forexample, its opacity at a single wavelength or its color, is changed asa consequence of a chemical reaction that occurs in the presence of amolecular species of interest. A further object, therefore, is toprovide a molecular species detector wherein changes in characteristicsof a material are effected in the presence of a molecular species ofinterest and such changes are sensed to determine the presence of thespecies and the amount of that species of molecule present.

In such a detector the chemical reaction that changes the materialcharacteristic of interest has a relatively short time constant (τ_(c)herein); there is also a chemical deterioration of the material over alonger period of time (τ_(o) herein) and in the system disclosed, thatdeterioration is counteracted.

Another object is to provide a molecule detector wherein saiddeterioration is periodically counteracted to reset the detector.

Still another object is to provide a detector of the foregoing type forin vivo use.

The literature abounds with writings delineating the need for systemsfor detection of O₂, CO, CO₂, NO, NO₂, SO₂, OH⁻, F⁻, H₂ S, H₂, HCl, D₂,CN, etc. Such systems may be used, by way of illustration, to measurethe level of pollutants in an air environment, or in the exhaust fumesof a motor vehicle, or a smokestack. There is need, as well, to measureoxygen levels or carbon monoxide levels in vivo without removing samplesof blood or tissue from the body of a person; and there is need to sensethe presence and the amount of other small molecules in the blood ofsuch person.

Another object is to provide a detector which can sense the presence ofa species of small molecule in a fluid environment and can give anindication of the partial pressure thereof, in the atmosphere, in vivo,and in other environments.

In certain chemical processes, precursors of a product are passedthrough a column containing an enzyme or other catalyst under controlledconditions; the precursors react within the column in the presence ofthe enzyme or other catalyst which itself undergoes an aging process.

Still another object of this invention is to provide a way to reversethe aging process of enzymes or other catalysts.

Still another object is to inactivate viruses, microbes and certainproteins.

Still another object is to provide a way to preserve a material againstoxidation and/or aging, e.g., certain tissues, gametes and otherbiomaterials.

Still another object is to accelerate the aging process of certainmaterials such as, for example, microorganisms, hemoglobin (to formmethemoglobin, as may be used in a cyanide detector).

Still another object is to restore chemical catalysts or reagents whichage and, eventually, if left alone, cease to be functional.

Still another object is to protect materials from oxygen, e.g.,biopolymers such as nitrogenase wherein oxygen inactivates the activesite.

Still another object is to maintain materials in a pseudo-living stateand to use them in that state for molecule detection and chemicalsynthesis.

These and still further objects are discussed hereinafter and areparticularly delineated in the appended claims.

The objects are achieved in a process wherein a chemical change wroughtupon a material is reversed by injecting appropriate electrical chargecarriers into the material to counteract unwanted deterioration thereofand cause the material to revert to a desired state; or the injection ofsuch carriers can be effective to maintain the desired state of amaterial that would otherwise undergo chemical change.

The invention is hereinafter explained with reference to theaccompanying drawing in which:

FIG. 1 is a schematic representation, partly block diagram in form,showing a resettable detector system to sense the partial pressure of amolecular species in a fluid and includes a radiation source andradiation sensor, two electrodes and a material through which theradiation passes and which modifies the radiation;

FIG. 2 is an enlarged isometric view, partly cutaway, showing apractical embodiment of a molecular species detector that may be used invivo;

FIG. 3 shows, schematically and partly in block diagram form, a detectorlike the detector in FIG. 2, and pulse-interval-modulated analyzingcircuitry to provide an indication of the partial pressure of amolecular species of interest in the environment about the detector;

FIG. 4 shows schematically a system wherein the analyzing circuitrydiffers from that in FIG. 3 (i.e., the circuitry of FIG. 4 is frequencymodulated), but the detector is similar to that of FIG. 3;

FIG. 5 is an isometric view of the portion of a detector, like thedetector of FIG. 1, and is intended to emphasize the electrodes and anion exchange membrane;

FIG. 6 is an isometric view, greatly enlarged, of a molecular speciesdetector having two radiation sources and two sensors, but, for clarity,the material between the sources and the sensors and other parts areomitted;

FIG. 7 shows a molecule detector, like the detector of FIG. 1, butemploying transducers that differ from the optical radiation source andradiation sensor of FIG. 1;

FIG. 8 is an isometric section view, partly cutaway and diagrammatic inform, showing one section of a catalytic system wherein a substrate isreacted in the presence of a catalyst to provide a product, the catalystbeing resettable in the same manner as is the material in the system ofFIG. 1;

FIG. 9 is an isometric view of a modification of the section of FIG. 8;

FIG. 10 shows a plurality of sections, like the section of FIG. 9 intandem and, it shows, schematically, associated system elements;

FIGS. 11A and 11B are partial isometric views of modifications of thesection in FIG. 8;

FIG. 12 is a side section view of a further modification of the sectionof FIG. 8; and

FIG. 13 is a schematic representation, partly block diagram in form of asystem wherein solar radiation under controlled conditions is employedto produce protons (H⁺), wherein the protons convert to H₂, and whereinthe material wherein the H₂ is formed is periodically reset.

To avoid confusion, in this specification two phenomena that appearthroughout the discussion should be distinguished. In the molecularspecies detector herein disclosed, one or more characteristics of amaterial (e.g., the optical density of the material) change in thepresence of the molecular species of interest; that change incharacteristics occurs because of what is termed herein a chemical"reversible binding" and is an effect having a short time constant(τ_(c)). There is another effect that is long range (i.e., characterizedby a typically long time constant (τ_(o)) and is referred to throughoutthis specification as "deterioration"; deterioration is a degradingeffect upon the material by virtue of the environment within which thematerial is placed, leading to progressive insensitivity toward thespecies of interest. Thus, with respect to the molecular speciesdetector hereinafter described the term "reversible binding" refers tothe reversible chemical binding, e.g., oxygenation, between the speciesof interest and the active material of the detector (e.g. the formationof oxygenated hemoglobin (i.e., oxyhemoglobin) when the material ishemoglobin) whereas deterioration is a long range opacity that set inbecause of the environment (e.g., the formation of Fe⁺⁺⁺ due to theoxidation of the hemoglobin). The reversible binding, e.g., oxygenation,effect is a direct function of the partial pressure or amount of thespecies of interest in the vicinity of the sensing material and thematerial reverts to its original state if the species of interest isremoved in direct proportion to the amount removed. The deteriorationeffect does not revert just because the species of interest is removed.In the enzyme catalytic system later described, "reaction" refers to theactions upon a substrate to produce a product, whereas "deterioration"refers to degradation of the enzyme due, in part, to the catalyticreaction but also to the environment in general.

The apparatus shown diagrammatically at 101 in FIG. 1 is a molecularspecies detector system which senses the partial pressure of a molecularspecies in a fluid environment. The detector system 101 comprises adevice 102 that includes a radiation-transmitting material 1 whoseoptical density changes at specific wavelengths of electromagneticradiation when said material is exposed to the molecular species ofinterest, by virtue of reversible binding of the molecules of thespecies. A light emitting diode or other radiation source 3, energizedby a current source 4, generates radiation at a predetermined frequencyand that radiation passes through the material 1 to a radiation sensor 5to provide a current output that bears a relationship to the intensityof radiation received. The radiation source 3, the material 1, and theradiation sensor 5, as shown in FIG. 2 and the other figures herein,form a unitary structure wherein the three elements just named bear afixed mechanical relationship to one another in order that the output ofthe radiation sensor 5 be a continuous function of the intensity of theradiation received, as just noted, and not include a component due toother irrelevant factors. The electric current output of the sensor 5 isconnected to electrical circuitry 103 that includes analyzing circuitry6. Any change in the density of the material 1 as a consequence of saidreversible binding results in a change in the intensity of the lightstriking the sensor 5, thereby causing a change in the output current ofthe sensor 5. The electrical circuitry 103 (which can include anappropriately calibrated ammeter) notes the current and relates it tothe partial pressure of the molecular species in the fluid. (Thus, thesystem 101 consists of a species detector 102 that includes the material1, the LED 3, sensor 5, etc., and the outside electrical circuitry 103.)Radiation transmission, as later explained, of the material 1 is alsoaffected by an aging process whereby the opacity of the materialincreases as a function of time. Periodically, the material 1 is resetor caused to revert to its original state, as now explained with respectto a system wherein the material 1 includes an emphore, that is, thematerial consists of molecules which are capable of enzymatic effectupon the emphore. (See the Pardee article previously mentioned for adefinition of emphores.)

More specifically, the material 1 at this juncture is a composite orresultant material that includes a gelatin binder containing hemoglobinto form a matrix material, a dye such as methylene blue that serves asan electroactive mediator, and small amounts of a plasticizer, such asglycerin to prevent drying; and the molecular species sensed is oxygen(see the accompanying writing entitled "An Oxygen Partial PressureSensor with Reset"). The diode 3 in an actual system is a light emittingdiode (e.g., Motorola MLED-455); the LED used emits radiation at 660 to680 nanometers. The detector is a back biased equivalent diode, but canbe a photoconductor, phototransistor, photofet, or other opticaldetector. Hemoglobin contains the transition metal iron which is theactive chemical element in the sensing system and enables the material 1reversibly to bind small molecules. Initially, the material is red; asoxygen diffuses into it the color changes by a process of oxygenation toorange (oxyhemoglobin) and, more slowly, by oxidation, to brown(methemoglobin). The orange color results from the oxygenation processwherein the transition metal, iron, remains in the form Fe⁺⁺, where asoxidation produces methemoglobin wherein the iron is in the Fe⁺⁺⁺ form.The oxygen partial pressures (P_(o).sbsb.2 herein) in the environmentdetermines the amount of the material 1 that changes to orange and it isthe determination of that amount, optically, that indicates theP_(o).sbsb.2 level.

After some time has passed, the Fe⁺⁺⁺ reaches a level wherein the sensorceases to function accurately and must be reset. Periodically (e.g.,several time a day in the particular case depicted in FIG. 1 andemploying hemoglobin) a master controller 7 (e.g., a microprocessor)de-energizes the analyzing circuitry 6, but not the circuitry to the LED3, and connects the electric current source 4 across electrodes 8A(i.e., the anode) and 8B (i.e., the cathode) to pass an electric currentthrough the material 1. Electrons thereby introduced counteract theoxidation that has occurred in the transition metal, that is, the activeelement or elements in the material 1. In other words, the electronsthereby introduced to the material 1 act to reduce it to its originalstate. The dye permits the electron transfer between the electrodes 8Aand 8B and the emphore in the material 1. During the reset cycle, thediode 3 continues to radiate into the material 1 to create excitedelectronic levels of the dye so as to permit charge carrier transferthereto. To place some perspective on the system just described, thevoltage developed between the electrodes 8A and 8B in actual apparatus,is about three volts (this is a function of device size) to perform thereset function. The combined effect of the electroactive mediator (i.e.,the dye) and the proper radiation is to permit introduction of thecharge carriers to the hemoglobin at an applied electric potentialdifference that minimizes the electrolysis potential of the resultingmaterial 1. As hereinafter explained, an ion exchange membrane 2 servesto create a uniformly reduced hemoglobin over most of the bulk of thecomposite material 1 so as to render most of the volume between theelectrodes 8A and 8B effective for charge injection. The layer labeled 9is a layer of oxygen permeable material (e.g., Teflon or Silicone) toprevent contamination of the active sensing elements. The gelatin may becommercially available product (e.g., Knox gelatin).

The system just described is useful to sense O₂ (˜670 nanometers), CO(˜815 nanometers), cyanide (˜900 nanometers) and NO₂ (˜960 nanometers).Further systems employing different active elements and differentradiation frequencies can be used to detect other small molecules. Thepartial pressure of the molecular species just mentioned can be found inair, but it can be determined, also, when the fluid is a liquid, e.g.,blood. Hence, the system 101 can function to monitor O₂ or CO in bloodor other tissue, in vivo, the interpreting circuitry being conencted totelemetry circuitry, for example.

In the system 101 just described the gelatin serves to entrap or bindthe hemoglobin; hydrophilic additives such as glycerin act as a dopantto prevent drying and, hence, minimize denaturation. The polyenecatalyst methylene blue, which is an electroactive mediator in thesystem, as above noted, can be replaced by other dyes in some systems,and, in general, the electroactive mediator is chosen from the groupconsisting essentially of dyes, quinones, free transition metals andother molecules with conjugated π-electrons. The detectors can be aphoto-FET or a back-biased LED or the like of appropriate frequencysensitivity, as above noted. The emphore hemoglobin is used to sense O₂,CN, NO₂ and CO; Vaska's compound (i.e., iridium bis-(triphenylphosphine) carbonyl halogen) can be used to sense SO₂, O₂, H₂,tetrafluoroethylene and D₂.

As above noted, the small molecules of greatest interest are O₂, CO₂,CN, CO, NO, NO₂, SO₂, H₂ S, H₂ D₂, OH⁻ and F⁻ ; to function inaccordance with the present teachings, the material 1 must reversiblybind to the small molecule to-be-detected. In the case of oxygen, thematerials of greatest interest are oxyemphores (i.e., oxygen-bindingemphores) that are taken from the group consisting essentially ofiron-containing emphores (e.g., hemoglobin, hemerythrin, myoglobin,erythrocruorin, chlorocruorin, dimethylglyoxime, bis-indigo, syntheticporphyrins, capped porphyrins, etc.) copper-containing emphores (e.g.,hemocyanin), nickel-containing emphores (e.g., dimethylglyoxime),cobalt-containing emphores (e.g., dihistidine, diglutamic acid,bis-salicylaldehyde ethylene diimine, diglycine, vitamin B₁₂,coboglobin, pentamine, etc.), iridium-containing emphores (e.g., iridiumcontaining Vaska's compound and congeners, and cis-1, 2-bis [diphenylphosphine] ethylene), platinum-containing emphores (e.g., platinum bistriphenyl phosphine) and manganese-containing emphores (e.g., pthallocyanine, etc.); in the list of oxyemphores just given, the metal namedis the transition metal. Other small molecules and reversibly-bindingmaterials 1 that are used therefor, are given in the next paragraph.

For CO, a useful material 1 contains an emphore taken from the groupconsisting essentially of hemoglobin, iron dimethyl glyoxime, andiridium cis-1,2-bis (diphenyl phosphine) ethylene. When the smallmolecule is SO₂, HCl, H₂ and D₂, said material 1 contains an emphoretaken from the group consisting essentially of iridium chlorocarbonylbis-triphenyl phosphine, and iridium cis 1, 2-bis diphenyl phosphineethylene and their congeners. For cyanide (CN), said material containsan emphore taken from the group consisting essentially of hemoglobin andiron dimethyl glyoxime. As for the small molecules NO, NO₂, F⁻ and OH⁻,the material 1 is one that contains hemoglobin.

The time τ_(R) to return the material 1 to its original state, that is,to accomplish the reset function is found from the following expression:##EQU1## wherein Σ is the molar sum of all oxidized constituents in saidmaterial, κ is the electric current through the material in microamperesand η_(R) is the efficiency of the reduction process. Ideally τ_(R)<<τ_(o), the oxidation time.

To enlarge somewhat upon the above discussion, the transition metalatoms that can be used in the system include Group VIII elements of theperiodic table, copper and zinc, but metals of the lanthanide andactinide series can also be used. The deterioration mentioned can beoxidation of the transition element, as is the case above, or it can bereduction of the transition element; in the first case reset isaccomplished by injecting electrons into the emphore or other matrixmaterial and in the latter holes are injected. The binding materialsthat may be used include gelatin, agar, ion exchange resins, acrylimidegel, styrenes, starches, glasses, clays, methacrylates, nylons,magnetite, nickel oxides, and other polymers. The anti-dessicantsubstances that can be employed to prevent drying include glycerin(i.e., glycerol), dimethyl sulfoxide, trimethylamine, and ethyleneglycol. Useful electroactive mediators includes dyes (e.g., methyleneblue, meta-tolulene diamine indophenol, carotene), quinones, freetransition metals (including free copper and zinc), and other moleculeswith conjugated π-electron systems, as well as other elements andcomplexes with d⁻ and f⁻ electrons capable of moving between two or moreelectronic states.

In addition, the material 1 can contain trace amounts of antibiotics toprevent destruction of the material from microbial growth; suchantibiotics are taken from the group consisting essentially ofamphotericin B, streptomycin, penicillin, mercurials, and theircongeners.

As noted above, an emphore is a molecule that is capable of a reversiblecombination with another molecule, but there is no net chemical orenzymatic effect upon either the emphore or the other molecule which isbound. Living systems have evolved many such emphores; some reside intissues and are responsible for the distribution of gases: e.g.,hemoglobin in vertebrate blood, hemocyanin in molluscs, and myoglobin instriated muscle. Other emphores are used to protect living systems frominfections and toxins (e.g., antibodies); others are used fortransportation of metals (e.g., ceruloplasmin for copper and transferrinfor iron), still others stabilize tissue levels of hormones and vitamins(e.g., thyroid binding globulin and intrinsic factor for vitamin B₁₂).Other emphores are used for the construction of proteins from theirconstituent amino acids (e.g., transfer RNA and sub-units of theribosome) and for ultimate control of DNA (e.g., the repression oractivation of genetic operons). These further emphores can be employedin systems wherein a molecular species sensed is not a small molecule(i.e., ≦100 Daltons) as above but also in a system wherein a molecularspecies sensed comprises macromolecules (i.e., ≧100 Daltons), to whichthey bind (e.g., antigens, Fe, Cu, CEA, vitamin B₁₂, thyroid hormone,DNA).

In such a large molecule detector said material 1 contains antibodieswith specificity for the large molecule of interest. The antibodies aretaken from the group consisting essentially of immunoglobin classes A,G, M, D and E. In such a detector, the means for detecting again maycomprise optical means operable to detect any changes in the opticaldensity of the material, the antibodies being specific for a particularantigen and being immobilized alone or with dyes and/or transitionelements in a layer to yield a material wherein the optical density at agiven wavelength changes with the binding thereto of the particularantigens (e.g., carcinoembryonic antigen, ceruloplasmin, components ofB-streptococcal wall, human chorionic gonadotrophin (HCG), thyroidbinding globulin, thyroid hormone, insulin, parathormone, etc.).

The above explanation is made with reference to the preferred embodimentof the molecule detector apparatus which uses light as a sensingingredient as well as a mechanism to enable the reset aspects. It shouldbe noted that changes in other properties of the material 1 can besensed, as well. Thus, with reference to FIG. 7, a molecular speciesdetector 102B is shown again comprising a material 1 with electrodes 8Aand 8B serving the same purpose as before; again an ion exchangemembrane is used, but is not shown in FIG. 7. The elements shown as 3Band 5B in FIG. 7 are transducers, the first being an input transducerand the second being an output transducer. Thus, if the transducer 3B isan acoustic transducer that introduces high frequency phonons (see U.S.Pat. No. 3,871,017, Pratt, Jr.) to the material 1, which phonons arereceived by the sensor transducers 5B, changes in the intensity of thereceived phonons can be used as an indication of changes in the material1 because of the presence of the molecule-of-interest in the environmentand changes in the phonon intensity indicate the partial pressure of themolecule-of-interest. Also, injection of appropriate high frequencyphonons in combination with an appropriate electroactive mediator in thematerial 1, serves to enhance charge carrier transfer thereto.

Also, the transducers 3B and 5B can be respectively means forintroducing a magnetic field to the material 1 and magnetic sensor andthe material 1 can be one whose magnetic properties change in thepresence of the small molecule of interest and in proportion to thepartial pressure of that molecule. For example, the Fe⁺⁺ in thehemoglobin detector is magnetic and the magnetic properties of thematerial 1 in such detector change in response to O₂, the environment inthis case being diamagnetic. Or the transducers 3B and 5B can beelectrical.

A practical embodiment of a detector device that may be fabricated isshown at 102A in FIG. 2 comprising a metal or plastic cap 10, an oxygenpermeable membrane 9A, and an oxyemphore composition or material 1.Conductors 12 and 13 connect to the electrodes 8A and 8B, leads 14 and15 connect to the LED 3 and the sensor 5. The electrical, optical anddiffusive axes in the device 102A are the z, x and y axes, respectively,and represent in the systems herein disclosed, the electron flowdirection, the light propagation direction and the diffusive path forthe molecular species, respectively.

The device 102A can be constructed within a transistor header. Theoxygen permeable membrane 9A covers the otherwise enclosed oxyemphorematerial 1 and preserves it from contamination. In an operating system,oxygen diffuses along the diffusive axis; radiation from the embeddedLED is directed along the optical axis to the embedded sensor which canbe a back-biased LED, as before. To reset the device, current flows intothe conductor 12 to the electrode 8A, the material 1, the electrode 8Bto the conductor 13 which is ground G (which is a common return path forall circuits here and in FIG. 3). A temperature sensor 17, energizedthrough conductor 16 to ground G, sends messages to the mastercontroller 7 in FIGS. 1 and 3 along a conductor 18. The device 102A canbe calibrated in known ways using gases or the like having known partialpressures (see, for example, U.S. Pat. No. 3,826,920, Woodroffe et al);it is sensitive to temperature changes; hence the temperature sensor 17is employed to compensate for changes in temperature.

The circuit shown in some detail in FIG. 3 is one that the inventor hasused to detect partial pressures in gases; it is shown mostly forenabling purposes and need not be explained in great detail. Thecircuitry in FIG. 4 is particularly adapted to in vivo uses; theinductance labeled L₁ can serve as an antenna to provide weak RF signalsthat can be picked up and interpreted by a small receiver (not shown) ona person's wrist, for example. In said accompanying writing there aredescribed devices built within dual-in-line packages wherein a material,like the material 1, is placed within said packages and between theLEDs. An ion exchange membrane is used (for purposes discussed elsewhereherein); and platinum mesh is employed to define the electrical axis.The whole of the active part is embedded in an epoxy (Tracon 2113) whichis a transparent, insulating and hydrophobic substance.

In the molecule detector labeled 102C in FIG. 6, the material 1 isomitted to simplify the figure, as is a cover like the cover 9A in FIG.2. Two radiation sources 3C₁ and 3C₂ and two radiation sensors 5C₁ and5C₂, respectively, are included in the detector 102C.

The detector 102C in FIG. 6 is a diagrammatic and enlarged view of adetector that embodies the present invention and is a modification of adetector type that was built and tested. A fourteen lead hybriddual-in-line package (Packing Unlimited CN5755) was used as a base uponwhich to construct the detector. Following an ultrasonic wash for oneminute in distilled water, bonds were made between the terminalsentering the packing and platinum mesh electrodes as well as red LEDs.The platinum mesh and the LED leads were soldered with an iridium alloysolder and flux. The units were later washed, again ultrasonically,photographed, and checked for continuity and independent working of eachLED (two each, in three packages). Later the unit was tipped at an angleby inserting some of the leads into clay. Epoxy (Tracon 2113) was pouredinto the package in two stages separated by two days to form a channelbounded by platinum mesh and two light emitting diodes.

A much smaller and more compact arrangement than that in FIG. 6 can beachieved by using semiconductor fabrication techniques already wellknown. Mesas are fabricated by etching a chip of GaAsP/GaAs. At hightemperature zinc (or tellurium, etc.) is made to diffuse into the mesascreating "p" regions. P-n junctions are then formed. If a groove is thencut, two p-n junctions with a common base are constructed; by thenpouring a transparent, electrically insulating layer (as Tra-Con 2113),a barrier will be formed between the monolithic sensor and its(to-be-poured) hemogel (i.e., hemoglobin entrapped in gelatin).Electrical attachment to the p and n regions is obtained at the ends ofthe monolithic device thereby fabricated.

Previous mention is made of the use of an anion exchange membrane in thesystems herein disclosed. With reference to FIG. 5, the anion exchangemembrane, again designated 2, is in electrical contact with theelectrode 8A and it affects the system in this way: in the absence ofthe membrane 2 there will be a buildup of oxidized material in thevicinity of the anode. With the membrane 2 present, reduction occursacross the bulk of the material 1.

The resetting concept disclosed herein can be used in other moleculedetecting systems such as, for example, the system disclosed in U.S.Pat. No. 3,873,267 of the present inventor, but it can be used in othersystems, too, as now explained, in connection with a system whereinenzymes or other catalysts are employed for chemical synthesis.

In the chemical synthesizing system shown schematically at 104 in FIG.8, a substrate S passes either by gravity feed (or by force feed througha side port) through an enzyme or other catalytic core material 20 toprovide as a product P (e.g., NH₃) in a chemical synthesis process thatis widely known and used: the process in FIG. 8 is represented by theexpression,

substrate+enzyme→substrate-enzyme complex→product-enzymecomplex→product+enzyme. In the course of such synthesis, the enzyme maybe subject to deterioration due to desiccation and due to changesincurred by the chemical synthesis process, as well as to oxidation, thelatter being transition metal oxidation and/or sulfhydryl groupoxidation; and the enzyme core 20 must be periodically upgraded. Allforms of deterioration are ameliorated in the system in FIG. 8 whereinthe enzyme material 20 that has become oxidized is reduced byintroducing electrons thereto in the manner before discussed. The anodein FIG. 8 is marked 8A₁ and the power source is a battery 40 (an anionexchange membrane is used in the system 104, as before, but is notshown). An electroactive mediator is added to the enzyme or othercatalyst 20, as before, to facilitate charge transfer. In FIG. 8, theprocess occurs within a tubular reaction member 21 which may be glass orplastic, for example; the substrate is introduced through entrances 22Aand 22B to the reaction member 21. The substrate S reacts with theenzyme contained in the material 20 (i.e., the material 20 is anappropriate enzyme plus an electroactive mediator, plus any requiredantidessicants, etc., as before, but the enzyme is the active part asfar as the substrate is concerned) to form the product P which diffusesthrough the walls of tubes 23 (which walls are permeable to the productbut not the material 20) and are removed from the system at the topand/or bottom as shown. In FIG. 8, the tubes 23 are shown at the top ofthe figures as open ellipses to represent hollow tubes, the elongatemembers 8B₁ are shown as solid ellipses to distinguish them from thetubes 23, the members 8B₁ being merely solid conductors that serve ascathodes throughout the length of the system 104. The two tubularmembers marked 25, and having dots at the upper ends of each todistinguish them from the cathodes 8B₁ and the tubes 23, are lossy lightpipes that receive light from a light source 24 and deliver it to thematerial 20 to irradiate the same for the reset purposes beforediscussed. A phonon generator 26 can be used to augment the light source24 and light pipes 25. The generator 26 is intended to represent phonongenerating transducers that may be embedded in the material 20 as wellas appropriate energizing means.

The system labeled 104A in FIG. 9 is coaxial. A substrate S isintroduced at the top of the system into a tube 23A of the system, itmoves downward under the pull of gravity, it diffuses radially throughthe walls of the tube 23A outward into an annular region occupied by amaterial again marked 20 that comprises an enzyme or other catalyst, aproduct P is formed; the product P diffuses into the tube 23A and out ofthe system as before. The material 20 is periodically reset tocounteract deterioration by passing a current between an anode 8A₂ and amesh cathode 8B₂. Details of the interior anode, cathode and an anionexchange membrane are omitted; however, it should be noted that theelectric field in FIG. 9 is transverse to the axis of the system, thatis, the field lines are radial in the system 104A. The walls of thetubes 23A are impermeable to the material 20.

The system shown at 104B in FIG. 10 is a serial system comprising two(or more) sub-systems 105A, 105B . . . in tandem. Substrate S isintroduced at the top of the system and a product exits from the bottom.The subsystem 105A is shown with control apparatus inluding a mastercontroller 7A (which may be or may include a microprocessor) that servesto direct the various system functions which include substrate flowcontrol through a valve 30. A sensor 32 notes product flow levels and,when the level of product flow drops below some predetermined level(which ordinarily will occur because of deterioration of the enzyme orother catalyst in the system), the master controller 7A energizes acurrent source 4A to introduce charge carriers into the enzyme or othercatalyst, as before. The master controller 7A can also close the valve30 to stop substrate flow. A voltage sensor 31 notes when the enzyme orother catalyst is renewed; it then turns off the current source 4Aand/or sends an appropriate message to the master controller 7A. Thesubsystems 105B . . . can be similarly served. A transducer 33introduces photons and/or phonons for the purposes previously discussed.In the tandem system 104B emission from the first and any intermediatestage is used as substrate for the next stage; and the emission from thelast stage is the final product.

The systems shown respectively at 104B and 104C in FIGS. 11A and 11B aremodifications of the system 104. The material is again marked 20 inthese two systems and again is an enzyme or other catalytic materialplus an electroactive mediator, etc. The material 20 occupies an annularspace between anodes 8A₂ and 8A₃ and cathodes 8B₂ and 8B₃, respectively.The electric field lines in FIGS. 11A and 11B are radial; the substrateis introduced at the top of the material 20 in the two figures and flowsdownward by gravity feed. In the usual system the charge carriersinjected are electrons to reduce the enzyme which has been oxidized inthe course of catalysis. The anion exchange membrane in FIGS. 11A and11B are marked 2A₂ and 2A₃, respectively.

The system marked 104D in FIG. 12 is a schematic representation ofimmobilized-enzyme, electrode-reduction-apparatus for forming ammoniafrom nitrogen. The substrate, nitrogen gas N₂, is introduced at the top,and the product, NH₃, leaves at the bottom, as shown. The materiallabeled 20A includes an azoemphore (i.e., a nitrogen binding material)which uses molybdenum and iron as its active elements, a gelatin binder,methylene blue as the electroactive mediator and a phosphate buffer.Currents through the composite 20A serves to renew the same; an anionexchange membrane 2A renders electroactive the region between themembrane 2A and the cathode marked 8B₅, for such purposes. The anode inFIG. 12 is designated 8A₅. The horizontal electric field between theanode 8A₅ and the cathode 8B₅ is marked E_(H) ; periodically the fieldE_(H) is removed and a vertical electric field E_(V) (by electrodes notshown) is applied to move the ammonium within the system downward at afaster rate than would occur by gravity alone. A cation exchangemembrane 35 serves a purpose similar to the membrane 2A, for the fieldE_(V) .

The resetting feature above described also has use in the systemsdescribed in a journal article in The Sciences, October 1975, pp. 25-30,entitled "A Source of Self-Sufficiency," (Gorman); the article describesa photosynthesis process for producing hydrogen and an organic solarcell. The present teaching is concerned with rejuvenating the materialin each system, as now explained with reference to FIG. 13 which shows asystem 105 for the production of hydrogen gas from H₂ O and using lightenergy. (The chlorophyll in the organic solar cell described in theGorman article can similarly be reset.) The system 105 compriseselectrodes 80 and 81 connected across a voltage source 61 that applies avoltage (˜1.0 volt) across a material 60A containing algae or extractsof algae, as shown; H₂ O is introduced into the system 105 as is, also,light (hv) to activate the active components of the algae in aphotosynthesis process. The products are O₂, protons (H⁺) and electrons(e⁻), as shown. The protons are pulled through a cationic exchangemembrane 62 by a voltage of the source 61 into a material 1A₆ thatcontains hydrogenase, an electroactive mediator, etc., and whichdeteriorates over time; periodically the material 1A₆ is reset and, inthe reset process, is subjected to light at an appropriate frequencysimilar to that used in hemoglobin rejuvenation. To reset, the voltagesource 61 is disconnected from the system and a current source isconnected between electrodes 8A₆ and 8B₆, as before, and light ofappropriate frequency is shown upon the material 1A₆ . An ion exchangemembrane 2A₆ is employed. H₂ gas is formed in the entire bulk of thematerial 1A₆. If the cation exchange membrane 62 is thin enough, theprotons will diffuse therethrough without need of the voltage source 61.

Further modifications of the invention herein disclosed will occur topersons skilled in the art and all such modifications are deemed to bewithin the spirit and the scope of the invention as defined by theappended claims.

What is claimed is:
 1. In a process wherein a chemical change is wroughtupon a material as a consequence of it having been subjected to areaction or reactions, which chemical change is an unwanted chemicaldeterioration resulting from a reversible reaction which can becounteracted by introducing appropriate charge carriers, electrons orholes, into the electronic states of said material, the further steps ofadding small amounts of an electroactive mediator to the material tofacilitate the charge carrier transfer to said electronic states, theresulting material being a matrix material and the electroactivemediator, said matrix material containing an inorganic catalyst used toeffect the chemical reaction in which changes in character in the courseof the chemical reaction are due to the environment within which theprocess occurred, introducing photons to the resulting material, theelectroactive mediator being one which permits, in the presence of saidphotons, charge carrier transfer to the resulting material at an appliedelectric potential difference that is below the electrolysis potentialof the resulting material, and applying an electric potential across theresulting material to inject appropriate charge carriers into theresulting material and into the electronic states thereof to counteractthe unwanted chemical deterioration and cause the material to revert toa desired state.
 2. A process as claimed in claim 1 wherein saidelectroactive mediator is taken from the group consisting essentially ofdyes, quinones, free transition metals and other molecules withconjugated π-electron systems as well as other elements and complexeswith d⁻ and f⁻ electrons capable of moving between two or moreelectronic states.
 3. A process as claimed in claim 1 wherein theelectroactive mediator is one which permits the charge transfer in thepresence of photons of a narrow range of frequencies and in which thephotons introduced are within that range.
 4. A process as claimed inclaim 1 wherein said deterioration is oxidation and wherein thereversion to a desired state is effected by reduction of the matrixmaterial by introducing holes to said electronic states.
 5. A process asclaimed in claim 1 wherein said reversible deterioration is reductionand wherein the reversion to a desired state is effected by oxidation ofthe matrix material by introducing electrons to said electronic states.6. A process as claimed in claim 1 wherein the electric potential ismaintained for a time τ_(R), wherein ##EQU2## wherein Σ is the molar sumof all oxidized constituents in said resulting material and k iselectric current in microamperes.
 7. A process as claimed in claim 6wherein τ_(R) <τ_(o), τ_(o) being the characteristic time of oxidation.8. A system that comprises, in combination: material means that issubjected to a reaction or an environment which effects or tends toeffect deterioration thereof by virtue of chemical processes, whichdeterioration is caused by a reversible reaction which can becounteracted by introducing appropriate charge carriers into theelectronic states of said material means, said material means containingsmall amounts of an electroactive mediator to facilitate introduction ofthe charge carriers into the electronic states of said material means,said material means containing an enzyme used to effect the chemicalreaction or reactions; means to contain the enzyme; means permitting asubstrate to come in contact with the enzyme to produce a product;porous means permeable to the substrate and to the product to enable theproduct to be removed from the region of the enzyme; means to subjectthe material means to an electric field of sufficiently high intensityto counteract said deterioration and cause the material means to assumeor to retain a desired state by the introduction of said charge carriersto said electronic states and yet sufficiently low in intensity andsufficiently high in efficiency that no substantial electrolysis occurs;and means to direct electromagnetic radiation upon the material means toenhance the effect of the electric field in introducing the chargecarriers to the electronic states.
 9. A system as claimed in claim 8that further includes anion exchange membrane means that serves toaffect the electric field profile, thereby permitting bulk change ofsaid material.
 10. A system as claimed in claim 8 wherein said materialis a composite material that contains small amounts of saidelectroactive mediator which permits and enhances charge transfer tosaid material means in the presence of the electric field and thepresence of phonons within a range of frequencies and which thelast-named means is adapted to direct phonons in said range into saidmaterial means.
 11. A system as claimed in claim 8 wherein said materialmeans contains transition metal composites which bind other molecules.12. A system as claimed in claim 8 wherein said means to subjectcomprises electrode means and electrical power source means connected toenergize the electrode means.
 13. A system as claimed in claim 12 inwhich the means to direct electromagnetic radiation upon the material isadapted to irradiate the electrode means as well.
 14. A system asclaimed in claim 8 that comprises an outer tube and an inner tube nestedand coaxially disposed within the outer tube, with a space therebetween,the enzyme being disposed in said space, the inner tube being operableto receive a substrate and being permeable to the substrate, thesubstrate thus passing through the inner tube to the enzyme in saidspace to produce a product, the inner tube being porous also to theproduct which diffuses back into the inner tube, said electric fieldbeing a radial field in the space between the two tubes.
 15. A system asclaimed in claim 14 that further includes a tubular ion exchangemembrane disposed in the space between the inner tube and the outertube.
 16. A system as claimed in claim 14 having means to create alongitudinal electric field along the inner tube to facilitate entry ofthe substrate into the system and or to facilitate extraction of theproduct.
 17. A system as claimed in claim 16 having means to introducethe enzyme into said space.
 18. A system as claimed in claim 17 whereinthe means to subject the material means to an electric field is a sourceof electric potential, that further includes means to sense the electricpotential that appears across said space and that further includesfeedback connections so that when the regeneration is complete theelectric potential is terminated.
 19. A method of controlling the agingprocess of a toxin subject to aging, which aging results from areversible reaction that can be counteracted by introducing appropriatecharge carriers into the electronic states of said toxin, thatcomprises: introducing methylene blue as an electroactive mediator tothe toxin to facilitate the introduction of charge carriers to theelectronic states thereof; irradiating the toxin further to facilitatethe introduction of charge carriers to the electronic states thereof;and applying an electric potential across the toxin to introduce thecharge carriers to the material and into the electronic states thereof,and wherein photons in the red region of the electromatic spectrum areintroduced to the toxin to enhance said charge carrier transfer to saidtoxin.
 20. A method as claimed in claim 19 wherein the aging process isaccelerated by changing said charge carrier.
 21. A process for producingH₂ gas from H₂ O that includes introducing H₂ O to an algae system inthe presence of light, which algae system, in the presence of light,separates molecules of H₂ O into O₂ molecules, protons (H⁺) andelectrons (e⁻), drawing the protons (H⁺) into a material that isoperable to add electrons (e⁻) to the protons (H⁺) to produce H₂ gas,which material is subject to chemical deterioration that can becounteracted by introducing appropriate charge carriers into theelectronic states of said material, the further steps of adding anelectroactive mediator to the material, the electroactive mediator beingone which, in the presence of photons, permits charge carrier transferto said electronic states at an applied potential that is below theelectrolysis potential of the resulting material, introducing photons tothe resulting material, and applying an electric potential across thematerial to introduce charge carriers thereto.
 22. A process forproducing H₂ gas from H₂ O that includes the steps of introducing H₂ Oto an organic system in the presence of light, which organic system, inthe presence of light, separates molecules of H₂ O into O₂ molecules,protons (H⁺) and electrons (e⁻), drawing the protons (H⁺) into amaterial that contains hydrogenase and an electroactive mediator, whichmaterial is operable to convert the protons (H⁺) to H₂ gas, saidmaterial being subject to reversible deterioration over time, andperiodically applying an electric potential across the material tointroduce charge carriers into the material, which charge carriers serveto counteract the reversible deterioration and reset the material. 23.In a system for producing H₂ gas from H₂ O, an organic solar cellcomprising an organic material that in the presence of solar radiationseparates molecules of H₂ O into O₂ molecules, protons (H⁺) andelectrons (e⁻), cationic exchange membrane means that can pass theprotons (H⁺) therethrough, a further material that contains hydrogenaseand an electroactive mediator positioned to receive the protons (H⁺)after passage through the cationic exchange membrane means and operableto add an electron (e⁻) thereto to produce the H₂ gas therefrom, saidfurther material being subject to deterioration over time, andelectronic power source means connected to inject charge carriers intothe further material, which charge carriers serve, in the presence oflight, to counteract said deterioration and reset the further material.24. An organic solar cell as claimed in claim 23 wherein the cationexchange membrane means comprises a cation exchange membrane that isthin enough to pass the protons (H⁺) therethrough without an externalfield applied thereacross.
 25. An organic cell as claimed in claim 23that includes voltage source means positioned to apply an electricpotential across the organic material and the cationic exchange membranemeans with appropriate polarity to cause the protons (H⁺) to drifttoward the cationic exchange membrane means and to diffuse through thecationic exchange membrane means into said further material.
 26. Anorganic solar cell as claimed in claim 23 wherein the organic materialcontains algae.
 27. An organic solar cell as claimed in claim 26,wherein the organic material contains extracts of algae.
 28. An organicsolar cell as claimed in claim 26 wherein the organic material containschlorophyll.
 29. An organic solar cell as defined by claim 23 whereinthe H₂ gas is formed in the bulk of the further material and wherein thepower source means comprises spaced electrodes positioned to inject saidcharge carriers into the bulk of the further material, there being anion exchange membrane interposed between one of the electrodes and saidfurther material.
 30. An organic solar cell as defined by claim 29wherein said charge carriers are electrons (e⁻) directed into the bulkof the further material.